1. Technical Field
The present invention relates to transfusible, platelet preparation retaining normal, inherent platelet functions without immunogenicity. More particularly, the present invention relates to isolated, non-immunogenic, functional platelets and a container and method for preparing the same in situ.
2. Prior Art
One of the problems encountered particularly with repeated transfusions of platelet preparations is the induction of antibodies against platelets in the host or recipient. This condition is known as alloimmunization. It is generally believed that this alloimmunization is caused by the passenger lymphocytes present in the platelet concentrates prepared by the standard procedure.
Inability of UV-irradiated lymphocytes to stimulate allogenic cells in mixed lymphocyte culture has been reported by Lindahl-Kiessling et al. (Int. Arch. Allergy, 41:670-678, 1971). In addition, recent reports have shown that it is possible to induce specific immunological unresponsiveness in either an allograft (as described in Lau, et al, Science, 2211:754-756, 1983 and 223:607-609, 1984) or in animals as described by Kripke (Immunol. Rev., 80:87-102, 1984) by treatment of the transplanted tissue or recipient with UV radiation. UV radiation of an allograft may thus prevent rejection through mechanisms that retain allograft function but minimize foreignness.
As noted above, repeated platelet transfusions often result in alloimmunization (Aster et al, Transfusion, 4:428-440, 1964 and van Leeuwen, et al, Transplant. Proc., 5:1539-1542, 1973). Since platelets do not contain class II major histocompatibility antigens (Dausset, et al Transplantation, 4:182-193, 1966), which are believed to initiate the recognitive phase of the immunologic response, it is likely that the contaminating lymphocytes in platelet preparations produce the sensitization reaction (Welsh, et al, in Eur. J. Immunol., 7:267-272, 1977; Class, et al, Exp. Hematol., 9:84-89, 1981 and; Hartzmann, et al, Transplantation, 11:268-273, 1971). Prevention of platelet alloimmunization by cyclosporin treatment or by direct UV-irradiation of platelets has been recently reported by Slitcher et al, (Blood, Vol 64, No. 5, Suppl 1, 231a, 1984). However, there is no disclosure whatsoever as to the functional integrity of such UV-treated platelets as described by Slitcher et al. Furthermore, such direct exposure of platelets to UV irradiation in open containers is undesirable both because of loss of sterile conditions resulting therefrom and because of additional step of manipulation of these platelets prior to being in a condition suitable and ready for transfusion. In contrast, the process of the present invention makes it possible for the first time to obtain non-immunogenic, functional platelet concentrate ready for transfusion while kept stored in a suitable container, preferably a plastic bag, without further manipulation.